July 26, 2010 -- More than 75% of men diagnosed with low-risk prostate cancer undergo aggressive treatment -- either complete removal of the prostate or radiation therapy, according to a new study.

That's true, the researchers found, even in men with a low level of prostate-specific antigen (PSA) of under 4 nanograms per milliliter, one of the factors taken into account when treatment decisions are made.

"If we knew for sure everyone with a PSA under 4 would not die of prostate cancer, case closed," says researcher Mark N. Stein, MD, a medical oncologist at The Cancer Institute of New Jersey and assistant professor of medicine at the UMDNJ-Robert Wood Johnson Medical School, New Brunswick.

But that's far from true, Stein says. And that makes the balance between overtreatment and undertreatment difficult, he says. The report is appears in the Archives of Internal Medicine.

"The tremendous improvement in survival has been attributed to early detection and treatment," Stein and his colleagues write. "However, there have been concerns about the potential overdiagnosis and overtreatment of localized prostate cancer."

In the study, they looked at data from nearly 124,000 men with newly diagnosed prostate cancer from 2004 to 2006 to determine which men received aggressive treatment.

More than 192,000 new cases of prostate cancer were diagnosed in 2009, according to the American Cancer Society, and more than 27,000 men died of it.

Prostate Cancer Treatment Patterns: A Closer Look

Stein and his team looked at data from the SEER database, which drew from 16 tumor registries and covers about 26% of the U.S. population.

In all, 14% of the men had a PSA of 4 nanograms per milliliter or lower.

The PSA test measures prostate-specific antigen, a protein produced by the prostate. Typically, the higher the PSA level, the higher the risk of prostate cancer, although some men can have an elevated PSA without cancer and some men can have cancer without an elevated PSA. Most healthy men without prostate cancer will have a PSA of less than 4 nanograms per milliliter, so that level is a general cutoff as to whether to proceed to biopsy, although some say the threshold should be lower and adjusted for age.

Fifty-four percent of the men diagnosed with prostate cancer with a PSA at 4 or lower had low-risk disease, they found. That was also defined as being at stage T2a or lower, with a Gleason score of 6 or lower. A Gleason score, Stein says, is based on "how the cancer looks under the microscope." Scores of 8-10 (10 highest possible) are high-grade tumors, according to the American Cancer Society.

More than 75% of these men with so-called low-risk disease got aggressive therapy, Stein found -- either radical prostatectomy, complete removal of the gland, or radiation therapy.

The decisions are difficult, Stein tells WebMD. "Guys with PSAs under 4 could have lethal cancers," he says.

"These results underscore the fact that PSA level, the current biomarker, is not a sufficient basis for treatment decisions," the researchers write. What's needed, Stein says, are other markers -- such as specific genetic signatures tied to higher-risk disease -- to better predict the risk of a lethal cancer.

Aggressive Prostate Cancer Treatments: Other Opinions

The new research adds statistics to what has long been known, says Stuart Holden, MD, medical director of the Prostate Cancer Foundation and head of the Louis Warschaw Prostate Cancer Center at Cedars-Sinai Medical Center, Los Angeles, who reviewed the study for WebMD.

"This article is saying that PSA when used alone as a screening tool will tend to uncover many cancers that are harmless and do not need to be treated," he says."However, it will also discover some that do need to be treated."

Aggressive treatment for low-risk cancers is due, he says, to the lack of knowledge experts still have about prostate cancers, Holden says. It's not always possible to distinguish between harmless and aggressive cancers.

Another expert agrees prostate cancer is often overtreated. "There's no question there is a problem of overtreatment of prostate cancer," says Matthew Cooperberg, MD, assistant professor of urology at the University of San Francisco, who has published on the topic of low-risk prostate cancers.

"I think the authors are slightly unfair in their estimation of our ability to risk-stratify the disease and target treatment appropriately," he tells WebMD, noting that doctors take into account other factors besides the PSA level when deciding on the best course of treatment, such as age and other medical tests.

In a commentary accompanying the study, Richard Hoffman, MD, of the University of New Mexico and Steven Zeliadt, PhD, of the University of Washington point out that "once a man is diagnosed as having an early-stage cancer, regardless of his age, he faces a treatment decision."

More recently, however, the commentary writers say, another option has been proposed. Called active surveillance, it involves deferring treatment and monitoring the disease closely. It's a more aggressive approach than the previous and similar approach called watchful waiting, Stein tells WebMD.

"Instead of immediate treatment for men with low-risk disease, active surveillance involves monitoring the cancer by PSA testing and DRE [digital rectal exam] every 3 to 6 months and performing prostate biopsies every 12 to 24 months," the commentary authors write.

SOURCES: Mark N. Stein, MD, medical oncologist, The Cancer Institute of New Jersey; assistant professor of medicine, University of Medicine and Dentistry of New Jersey --Robert Wood Johnson Medical School, New Brunswick.